Process for preparing esters of pyridine thiones



United States Patent This invention relates to a process for thepreparation of esters of pyridinethione derivatives. More particularly,this invention relates to a method in which the sodium salt of a1-hydroxy-2-pyridinethione compound is reacted with a fatty acidanhydride to form in high yields the corresponding fatty acid ester.

The yield of the esters formed by the novel method of this invention isfrom 80 to 90 percent or more as compared to about 35 percent formethods known in the art for preparing these same compounds. advantageof this process is that it is carried out at tem peratures ranging fromabout 5 C. to about +30 C. thus avoiding the formation of undesirableside products which takes place at the temperatures utilized in theprior art processes, i.e. 80 90 C. Thus a purer product is obtained withthe method of this invention than with prior art methods since thereaction emperature is substantially decreased. The purity of theproducts of this invention is shown by the sharp melting points as wellas by the infrared spectra exhibited by these materials.

Therefore, the products produced by the process of this inventionrequire no recrystallization, while the same products, prepared by knownmethods, must be recrystallized for comparable purity.

In the process of this invention there is first prepared the sodium saltof a 1-hydroxy-2-pyridinethione compound by reacting sodium hydroxidewith the pyridinethione compound and then in a second step reactingsodium salt with a fatty acid anhydride under aqueous conditions. Thepotassium and lithium salts of the pyridinethione starting materials arealso useful.

The two-stage process of the present invention proceeds according to theequations'below where, for purposes of illustration, acetic acidanhydride is shown as the fatty acid anhydride:

Another 3,310,568 Patented Mar. 21, 1967 ice may be in tautomericequilibrium With the compound:

wherein R is hydrogen, alkyl of not more than 5 carbon atoms, alkoxy ofnot more than 5 carbon atoms or a halogen selected from the groupconsisting of chlorine, bromine and iodine and n is a positive intergerof no greater than four and preferably one.

Useful 1-hydroxy-2-pyridinethione compounds include, for example,l-hydroxy-2-pyridinethione, 1-hydroxy-3- methoxy-2-pyridinethione,1-hydroxy-5-butoxy-2-pyridinethione,l-hydroxy-3-methyl-2-pyridinethione, l-hydroxy-4,6-di-n-butyls2-pyridinethione, 1-hydroxy-3,4-dichloro-2-pyridinethione, 1-hydroxy-5-bromo-2-pyridinethione.

Suitable fatty acids whose anhydrides are utilizable as startingvmaterials in the process of this invention include: acetic, n-propionic,isopropionic, n-butyric, isobutyric, acrylic, crotonic and sorbic. Anyfatty acid anhydride yielding a water-soluble fatty acid is suitable forthe process of this invention.

Although the stoichiometric quantity of fatty acid anhydride can beemployed in this invention, preferably from about 3 to about 10 moles ofacetic anhydride are employed per mole of the sodium salt of thel-hydroxy-2- pyridinethione compound charged to the reactor. Generally,the temperature will range from about 5 C. to about +30 C. andpreferably will be from about 0 C. to about 15 C. If less than about 3moles of anhydride per mole of the pyridinethione compound areuntilized,

it has been found that a lower yield of a product exhibiting a lowermelting point than the preferred product is obtained. In the process ofthis invention the preferred pressure is atmospheric although pressuresranging from subatmospheric up to 10 atmospheres or more can be used.The reaction time will vary from about 0.1 to 3 hours or more dependingupon the particular reactants and reaction conditions utilized. 1

Recovery of the products of this invention, which are insoluble in thereaction medium employed, can be accomplished by filtration,centrifugation, decantation, etc.

The following examples which illustrate the process of this inventionare to be considered not limitative.

EXAMPLE I (A) Preparation of the sodium salt of l-hydroxy-Z-pyridinethione:

A solution of the sodium salt of l-hydroxy-Z-pyridinethione was preparedby neutralizing an aqueous slurry of 1-hydroxy-2-pyridinethione with 25percent aqueous sodium hydroxide until the pH of the resulting solutionwas in the range of 6.5 to 7.0, the sodium salt concentration was 12.5weight percent.

(B) Preparation of the acetate of l-hydroxy-Z-pyridinethione:

Five hundred grams of this solution (63 g. of the sodium salt .ofl-hydroxy-2-pyridinethione, 0.422 mole) was diluted with 500 grams ofwater and the solution then cooled to 0-5" C. To the cold solution, g.acetic anhydride (1.23 moles) were added and the mixture stirred at 0 to5 C. for 0.5 hour. The yellow product precipitate was then filtered out,washed several times with cold water, and dried for 16 hours in a vacuumoven at 50 C. The dried product (the acetate of l-hydroxy-Z-pyridinethione) weighed 64.3 grams (0.380 mole); M.P. 8888.5 C. Yieldwas 90.2 percent of the theoretical quantity.

The product was analyzed for carbon, hydrogen and sulfur and thefollowing results were obtained:

Analysis.Calcd for C H O NS: C, 49.70; H, 4.14; S, 19.95. Found: C,49.59; H, 4.43; S, 19.10.

EXAMPLE II Two hundred grams of an aqueous solution of the sodium saltof l-hydroXy-2-pyridin-ethione (0.097 mole) was diluted with 400 gramsof water and the solution cooled to C. To the cold solution 35 rnls.(0.343 mole) of acetic anhydride was added and the mixture stirred at 0to C. for 0.5 hour. The yellow product, which had precipitated from thereaction mixture, was then recovered by filtration, washed several timeswith cold water and dried for 16 hours in a vacuum oven at about 50 C.The dried product (the acetate of l-hydroxy-Z-pyridinethione) weighed0.075 mole which corresponds to a yield of 77.8 percent.

The product was submitted for infrared analysis and was shown to be pure1-hydroxy-2-pyridinethione acetate.

The esters of this invention are active bactericides and fungicides. Thefatty acid derivatives of this invention can, therefore, be used aspreservatives (for example, in leather, paper and fabrics) andespecially in paints and varnish to render them resistant against mildewor other fungus attack. In the protection of paints, for example, themixed anhydrides are simply mixed with the paint.

The mixed anhydrides of this invention find further use as agriculturalfungicides, the mixed anhydride being added either directly to the soil(by sprinkling the mixed anhydride itself or a composition of the mixedanhydride and suitable diluents onto the surface of the soil and thenthoroughly intermixing the soil and mixed anhydride) or directly toplant foliage by spraying a composition thereof with a suitable carrier.

What is claimed is:

1. A process for the preparation of an ester which comprises (A)neutralizing an aqueous slurry of a compound of the formula:

wherein R is selected from the group consisting of hydrogen, alkyl ofnot more than 5 carbon atoms, alkoxy of not more than 5 carbon atoms,and a halogen selected from the group consisting of chlorine, bromineand iodine,, and n is an integer no higher than four, with sodiumhydroxide until the pH of the resulting solution is in the range ofabout 6.5 to 7 whereby the sodium salt of the said compound is formedand (B) reacting the said sodium salt in aqueous solution with fro-mabout3 to about 10 moles of an anhyd-ride of a fatty acid selected fromthe group consisting of acetic, n-propionic, isopropionic, n-butyric,isobutyric, acrylic, crotonic and sorbic acid.

2. The process of claim 1 wherein the temperature of the reaction isfrom about 5 C. to about +30 C.

3. The process of claim 1 wherein the said anhydride is aceticanhydride.

4. The process of claim 1 wherein the said compound is: Y

I OH

5. The process of claim 1 wherein the said anhydride is aceticanhydride, the said compound is:

and the temperature of the reaction is from about 5 C. to about +30 C.

References Cited by the Examiner UNITED STATES PATENTS 2,758,116 8/1956Wiseogle et a1. -260.294.8

WALTER A. MODANCE, Primary Examiner.

ALAN L. ROTMAN, Assistant Examiner.

1. A PROCESS FOR THE PREPARATION OF AN ESTER WHICH COMPRISES (A)NEUTRALIZING AN AQUEOUS SLURRY OF A COMPOUND OF THE FORMULA: